1. Three Stages The process in which a signal on the outside of a cell is turned in to a specific cellular response on the inside of a cell is called a signal transduction pathway. –Reception: When a signal molecule binds to a specific protein on the plasma membrane. –Transduction: Relays the signal to the appropriate part of the cell. –Response: Could be anything from activating a gene, telling an NZ to work, etc.

3. More about the language Ligand- the molecule that is the chemical signal. Local signaling (short distance): the blood stream is usually not involved –Paracrine signaling: molecules other than neurotransmitters. –Synaptic: neurotransmitters Long distance: hormones. The blood stream is involved somehow

4. Four kinds of signal receptors 1)G-Protein-Linked Receptor Uses a protein called “G-protein” and is located on the plasma membrane Ligands can be hormones, epinephrine, neurotransmitters. The binding sites are different Acts like an on/off switch. If GDP (guanosine diphosphate) is attached to the inside portion of the protein, then the protein is “off” (inactive). If GTP (guanosine triphosphate) is attached to the inside portion of the protein, the the protein is “on” (active).

6. 2) Tyrosine-kinase receptors Primarily for growth factors; actually is two single parts Plasma membrane proteins with NZ portions on the cytosol side of the cell. Characterized by having enzymatic activity. NZ= tyrosine kinase. Takes phosphate from ATP and puts it on tyrosine of protein.

9. 3) Ligand-gated Ion Channels Extremely important in the nervous system!!! Helps or stops ions, such as Ca 2+, K + and Na +, from entering a cell. Located on the PM Ligand binds to the receptor. This causes the protein to open a tunnel (channel) down the middle. The channel allows ions to flow down into the cell. When the ligand leaves the receptor site, the channel will close.

11. 4) Intracellular Receptors In the cytosol (not PM). Ligands are HYDROPHOBIC steroid hormones, thyroid hormones and NO (nitric oxide, sometimes involved in aggressive behavior). Why would these need to be hydrophobic? Ligand diffuses into the cell, binds with the receptor protein. Then, the whole thing goes into the nucleus to turn “on” a gene. Testosterone- produced in testes, goes into bloodstream, enters a cell in the cheek of a 15 yr. old male, finds the specific receptor protein, the two go into the nucleus to turn “on” the gene for facial hair.

12. Transduction Pathways Why we have them? To get the message from the reception to the response. What are they? All of the messengers (chemical/molecule/protein) in between the receptor and the cellular response This could be one second messenger (a chemical/molecule/protein) after the receptor protein or several more The more messengers that are involved in a transduction pathway, the larger the cellular response is (especially with cascading phosphorylation)

13. Cascading phosphorylation An NZ will phosphorylate (donate a phosphate to a compound) a protein. An NZ that phosphorylates a protein from ATP is called a protein kinase. Once a protein is phosphorylated, it becomes activated. Then, the newly activated protein will become a protein kinase for the next protein in the pathway. One activated protein can become a protein kinase for several copies of the next protein in the pathway. Each protein kinase is specific for the next protein and only that protein (think structure and function) Protein phosphatases return the proteins to the “inactive state”

15. Response: glucose is released (10 8 )

16. Secondary messengers: –Non-proteins that are involved in transduction pathways. –Cyclic AMP: One of the two major secondary messengers Seen a lot with G-protein-linked receptors Adenylyl cyclase turns ATP into cAMP –Ca 2+ : Involved in the transduction pathways of nerve cells during muscle contraction (among many others) Regulated (turned off and on) by the Ca 2+ concentration. The cytosol is 10,000 times less concentrated than it surrounding areas.